LPS and proinflammatory cytokines decrease lipin-1 in mouse adipose tissue and 3T3-L1 adipocytes.
Infection and inflammation affect adipose triglyceride metabolism, resulting in increased plasma free fatty acid (FFA) and VLDL levels during the acute-phase response. Lipin-1, a multifunctional protein, plays a critical role in adipose differentiation, mitochondrial oxidation, and triglyceride synthesis. Here, we examined whether LPS [a Toll-like receptor (TLR)-4 activator], zymosan (a TLR-2 activator), and proinflammatory cytokines regulate lipin-1 in adipose tissue. LPS administration caused a marked decrease in the levels of lipin-1 mRNA and protein in adipose tissue. The decrease in lipin-1 mRNA levels occurred rapidly and lasted for at least 24 h. In contrast, lipin-2 and -3 mRNA levels did not change, suggesting specific repression of lipin-1. Zymosan similarly decreased lipin-1 mRNA without affecting lipin-2 or lipin-3 mRNA levels. To determine the pathways by which LPS repressed lipin-1, we examined the effect of proinflammatory cytokines on cultured adipocytes. In 3T3-L1 adipocytes, TNF-alpha, IL-1beta, and IFN-gamma, but not LPS or IL-6, caused a decrease in lipin-1 mRNA levels. Furthermore, TNF-alpha and IL-1beta administration also decreased mRNA levels of lipin-1 in adipose tissue in mice. Importantly, the LPS-induced decrease in lipin-1 mRNA levels was significantly but not totally blunted in TNF-alpha/IL-1 receptor-null mice compared with controls, suggesting key roles for TNF-alpha/IL-1beta and other cytokines in mediating LPS-induced repression of lipin-1. Together, our results demonstrate that expression of lipin-1, one of the essential triglyceride synthetic enzymes, was suppressed by LPS, zymosan, and proinflammatory cytokines in mouse adipose tissue and in cultured 3T3-L1 adipocytes, which could contribute to a decrease in the utilization of FFA to synthesize triglycerides in adipose tissue, thus promoting the release of FFA into the circulation.
Lu
Biao
B
Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, USA.
Lu
Yang
Y
Moser
Arthur H
AH
Shigenaga
Judy K
JK
Grunfeld
Carl
C
Feingold
Kenneth R
KR
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase; D012333:RNA, Messenger / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; D015054:Zymosan; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase